LFA-1-MEDIATED ADHESION IS REGULATED BY CYTOSKELETAL RESTRAINT AND BYA CA2-DEPENDENT PROTEASE, CALPAIN()

The activity of integrins on leukocytes is kept under tight control to avoid inappropriate adhesion while these cells are circulating in blo od or migrating through tissues. Using lymphocyte function-associated antigen-1 (LFA-1) on T cells as a model, we have investigated adhesion to ligand intercellular adhesion molecule-1 induced by the Ca2+ mobil izers, ionomycin, 2,5-di-t-butylhydroquinone, and thapsigargin, and th e well studied stimulators such as phorbol ester and crosslinking of t he antigen-specific T cell receptor (TCR)-CD3 complex, We report here that after exposure of T cells to these agonists, integrin is released from cytoskeletal control by the Ca2+-induced activation of a calpain -like enzyme, and adhesive contact between cells is strengthened by me ans of the clustering of mobilized LFA-1 on the membrane, We propose t hat methods of leukocyte stimulation that cause Ca2+ fluxes induce LFA -1 adhesion by regulation of calpain activity, These findings suggest a mechanism whereby engagement of the TCR could promote adhesion stren gthening at an early stage of interaction with an antigen-presenting c ell.